It is proposed to study the interaction of 4-nitroquinoline-1-oxide (4NQO) with the DNA of Bacillus subtilis. 4NQO is a bicyclic, water soluble hydrocarbon with potent carcinogenic properties. The mutagenic and lethal effects of this compound on the normal strain of Bacillus subtilis differ greatly from those resulting from treatment of repair- deficient mutants. The primary target affected by treatment with 4NQO is DNA. Bacillus subtilis is therefore an ideal organism for this study because it can be genetically transformed with single-stranded or double stranded DNA. We can therefore treat cells in vivo or DNA in vitro and study both of the treated DNAs by a variety of methods e.g. genetic, physico-chemical, and spectroscopic. We can therefore directly correlate molecular interactions and properties with biological manifestations. Wild type and mutant strains (defective in repair and recombination) will be treated with 4NQO, the fate of their DNA assessed, and products of their metabolism analyzed. Direct correlations of genetic and physiological manifestations to molecular interaction will be made through use of a broad approach. Techniques used are absorption spectroscopy, luminescence spectroscopy, polarization measurements, chromatography, physico-chemical, genetical, and other molecular biological techniques. We hope to provide a basic understanding of how the interaction of 4NQO and/or its metabolites and the chromosome leads to abnormal cellular conditions. These interactions are obviously linked to a variety of cancers, tumors, and mutations in mammalian tissue and to the lethal, mutagenic, and abnormal cell division in bacteria. B. subtilis, unlike some other bacterial species, has an aerobic metabolism and it will therefore metabolize more like mammalian tissue. Thus, proximate (true) carcinogens like those in mammalian cells can be formed in vivo. From these studies, we should receive data that will enable us to formulate a molecular model applicable to other chemicals affecting chromosomes. Tetra- or pentacyclic hydrocarbons, for example, would be expected to react similarly.